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WO2003059330A1 - Compositions pharmaceutiques stables comprenant un(des) inhibiteur(s) de l'enzyme de conversion - Google Patents

Compositions pharmaceutiques stables comprenant un(des) inhibiteur(s) de l'enzyme de conversion Download PDF

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Publication number
WO2003059330A1
WO2003059330A1 PCT/IB2003/000063 IB0300063W WO03059330A1 WO 2003059330 A1 WO2003059330 A1 WO 2003059330A1 IB 0300063 W IB0300063 W IB 0300063W WO 03059330 A1 WO03059330 A1 WO 03059330A1
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WO
WIPO (PCT)
Prior art keywords
composition
ace inhibitor
layer
core
pharmaceutically active
Prior art date
Application number
PCT/IB2003/000063
Other languages
English (en)
Inventor
Deepak Bahl
Ravi Kochhar
Puneet Sharma
Vishnubhotla Nagaprasad
Rajeev Shanker Mathur
Kamal Mehta
Original Assignee
Ranbaxy Laboratories Limited
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Ranbaxy Laboratories Limited filed Critical Ranbaxy Laboratories Limited
Priority to BR0306928-1A priority Critical patent/BR0306928A/pt
Priority to EP03729521A priority patent/EP1467717A1/fr
Priority to MXPA04006892A priority patent/MXPA04006892A/es
Priority to US10/501,450 priority patent/US20050202081A1/en
Priority to AU2003201071A priority patent/AU2003201071A1/en
Publication of WO2003059330A1 publication Critical patent/WO2003059330A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/55—Protease inhibitors
    • A61K38/556—Angiotensin converting enzyme inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/401—Proline; Derivatives thereof, e.g. captopril
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
    • A61K9/209—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat containing drug in at least two layers or in the core and in at least one outer layer
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/12—Drugs for disorders of the urinary system of the kidneys
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to stable pharmaceutical compositions comprising ace inhibitor(s), which are susceptible to degradation, and processes for the preparation thereof.
  • Angiotensin Converting Enzyme (ACE) inhibitors which are useful as antihypertensives, are susceptible to certain types of degradation.
  • ACE inhibitors such as ramipril, quinapril, enalapril, spirapril, lisinopril, benazepril and structurally related drugs can undergo cyclization via internal nucleophilic attack to form substituted diketopiperazines. These drugs can also degrade via hydrolysis (of the side-chain ester group) and oxidation, to form products having unwanted coloration. It has been found that a significant cause of such degradations can be the mechanical stress associated with the manufacturing process of pharmaceutical composition such as compression.
  • compositions containing ACE inhibitors can also be negatively influenced by the choice of tab letting auxiliaries.
  • ACE inhibitors In view of the usefulness of ACE inhibitors in treating hypertension, a number of research endeavors have been directed towards overcoming the inherent instability problem associated with ACE inhibitor- containing compositions.
  • United States Patent Nos. 4,743,450, 4,830,853, 4,793,998, international patent application WO 99/62560, European patent EP 468929 disclose stabilization with various agents.
  • United States Patent Nos. 5,151,433 and 5,442,008 disclose polymeric film-formers as protection against stress, as well as the use of buffers.
  • a stabilizer or a polymeric coat on the active ingredient is believed necessary to stabilize the pharmaceutical composition of ACE inhibitors, which are susceptible to degradation.
  • the addition of such stabilizers can produce unwanted pharmacological effects. Coating the active ingredient is quite cumbersome and low yielding moreover it requires specialized equipment. Summary The applicants of the present invention have discovered a process making the use of the above unnecessary.
  • Active ingredient for example, an ACE inhibitor, which is susceptible to degradation, is applied as a coat to the core, preferably to a compressed core, thereby avoiding degradation (such as cyclization to diketopiperazine) induced by mechanical stress, which builds up during compression.
  • ACE inhibitor which is susceptible to degradation
  • Such an arrangement also avoids the direct contact of the tabletting auxiliaries with the ACE inhibitor, thereby avoiding degradation by any incompatible tablet auxiliaries.
  • the present invention therefore allows greater flexibility in the choice of tabletting auxiliaries. Moreover, as stabilizers are not required, untoward pharmacological effects, which could occur with the addition of such additives, are nullified. The process can be easily scaled up using the conventional tabletting and coating equipment.
  • the present invention can provide a stable pharmaceutical composition for oral administration of an ACE inhibitor comprising a core coated with a layer of ACE inhibitor(s) and process for preparation thereof.
  • the core of the present invention is preferably a compressed core, which could be inert or may contain a drug other than the ACE inhibitor susceptible to degradation, such as hydrochlorotliiazide, piretanide; and dihydropyridines such as felodipine, nitrendipine, nifedipine, lacidipine or other similar drugs.
  • the core may be a sugar or starch particle such as non-pareil sugar seeds, or pregelatinized starch.
  • the core can be of any convenient shape, such as an spheroidal shape. The cores can range from about 25 mg to about 1 gram.
  • the compressed core may comprise diluent and other formulating agents such as binder, disintegrant, lubricant and glidant.
  • the diluent may be, for example, any pharmaceutically acceptable, non-toxic diluent. Particular examples include lactose, dextrose, sucrose, maltose, macrocrystalline cellulose, starch, calcium hydrogen phosphate, mannitol and the like.
  • Binders may be, for example, starch, sugars, gums, low molecular weight hydroxypropyl methylcellulose, hydroxypropylcellulose or the like.
  • Disintegrant may be, for example, croscarmellose sodium, crospovidone, sodium starch glycolate, bentonite, sodium alginate, hydroxypropylmethylcellulose or the like.
  • Lubricants may be, for example, talc, magnesium stearate, calcium stearate, hydrogenated vegetable oils, stearic acid, sodium stearyl fumarate, sodium benzoate or the like.
  • Glidants may be, for example, colloidal silicon dioxide (aerosil), talc or the like.
  • the ACE inhibitor layer comprises ACE inhibitor(s), which are susceptible to degradation, including ramipril, spirapril, lisinopril, enalapril, quinapril, benazepril and other structurally related drugs.
  • the process is applicable to other pharmaceutically active agents that are susceptible to mechanical stress-induced or mechanical stress-related degradation.
  • the ACE inhibitor can be micronized, and suspended/dispersed in a solvent to which film forming polymer(s) is added.
  • the film-forming polymer may be, for example, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxyethylcellulose, ethylcellulose, cellulose acetate, polyvinylpyrrolidone, gelatin, LustreClearTM (combination of microcrystalline cellulose and carrageenan), combinations of polyvinylalcohol and polyvinylacetate, and the like.
  • the amount of the film forming polymer(s) can be relatively low, to limit the tablet/pellet/beadlet size and the manufacturing effort, but should be sufficient to effectively coat the drug on to the core.
  • the drug to polymer ratio may range from about 1 : 10 to about 10:1.
  • drug to polymer ratio can be from about 1:2 to about 2:1, or from about 1:1.2 to about 1.2:1, or, for example, about 1:1.
  • the polymer that is used for binding properties can also protect ACE inhibitors from atmospheric or chemical oxidation and degradation by agents such as atmospheric humidity through, for example, hydrolysis.
  • the ACE inhibitor layer may optionally contain plasticizers, and is desirably without plasticizers. Stability can be undesirably lessened through the use of plasticizers.
  • Plasticizers which may be excluded from the compositions include polyethyleneglycol, propylene glycol, triethyl citrate, triacetin, dibutylphthalate, diethylphthalate, castor oil, tributyl citrate, glycerol, sorbitol, polysorbates, sorbitan esters and the like.
  • the ACE inhibitor layer may also contain pigments, colorants, antifoaming agents, waxes, monoglycerides, emulsifiers, surfactants or other additives.
  • the layer containing ACE inhibitor or other pharmaceutically active substance can contain such material from about 2% to about 90% by weight of the ACE inhibitor layer, and can also contain film-forming polymer from about 10% to about 98% by weight of the ACE inhibitor layer.
  • Drug coating solution can be prepared in water, non-aqueous solvents or mixtures thereof. However desirably in water as stability can be lessened through the use of non- aqueous solvents. Solvents that may be excluded are isopropyl alcohol, acetone andmethylene chloride .
  • a seal coat may optionally separate the core and the ace inhibitor layer to completely seal the tabletting auxiliaries to come in contact with the ACE inhibitor.
  • an outer coat may optionally be given on the ACE inhibitor layer to improve the aesthetic appeal of the tablet and to protect it from the atmospheric humidity.
  • the seal coat and outer coat may have the same composition as the ACE inhibitor layer except the drug, or it may have a different composition.
  • the seal coat may contain other polymers, such as Povidone.
  • the seal coat can be prepared from aqueous dispersion of from about 2% to about 30% by weight of film-forming polymer.
  • the process of the present invention may be carried out in the following manner.
  • the compressed core can be prepared by conventional techniques such as direct compression, wet granulation and dry granulation.
  • the ACE inhibitor coating dispersion, suspension or solution can be prepared by adding the active ingredient(s) in a solvent with stirring or other mixing. Film forming polymer(s) and other additives can be added to the active ingredient dispersion with stirring or other mixing.
  • the cores are charged into a coating pan and warmed with air to an outlet-air temperature of, for example, about 30°C-45°C.
  • the ACE inhibitor coating dispersion can be sprayed onto the cores and upon completion, the drug-coated tablets is dried, for example with dry air. Seal coat and outer coat dispersion may be prepared and applied in the similar manner as the ACE inhibitor layer, if required.
  • the coated tablets after air-drying can be packed into containers impervious to water vapor, e.g. blister packs (alu-alu; PVDC, PE, PVC-alu).
  • the tablets prepared by the present process may also be filed into capsules.
  • the present process may also be applied to the non-pareil seeds or beadlets, which may then be filled in hard gelatin or starch capsules.
  • Such capsules can have better stability as compared to the conventional capsules.
  • compositions disclosed herein may be formulated into solid dosage forms for oral administration, such as, for example, tablets, granules, capsules, pills, and the like.
  • the medicaments can be prepared by conventional methods, including a therapeutically effective amount of an ACE inhibitor or other pharmaceutically active substance, and optionally but desirably, pharmaceutically acceptable excipients.
  • the compositions may also be administered by controlled release means and/or delivery devices, with modifications known to those of ordinary skill in the art.
  • the compositions may, if desired, be presented in a pack or dispenser device, which may contain one or more unit dosage forms containing the active ingredient.
  • the pack may for example comprise metal or plastic foil, such as a blister pack.
  • the pack or dispenser device may be accompanied by instructions for administration.
  • terapéuticaally effective amount is meant the quantity of a compound or composition according to the invention necessary to prevent, cure or at least partially arrest the symptoms of the disorder and its complications. Amounts effective to achieve this goal will, of course, depend on the severity of the disease and the weight and general state of the patient.
  • compositions provided herein can be utilized for various treatment methods, such as those for treating hypertension, either alone or in combination with thiazide diuretics, as well as for use with stable patients who have demonstrated clinical signs of congestive heart failure within the first few days after sustaining acute myocardial infarction, and also for left ventricular dysfunction and diabetic nephropathy.
  • the methods include administering to a mammal a therapeutically effective amount of a pharmaceutical composition as described herein.
  • compositions can be by oral or buccal administration,. Other methods of administration will be known to those skilled in the art.
  • a convenient, reproducible stable pharmaceutical composition of the ACE inhibitors may be obtained.
  • the present invention is further illustrative by, but is by no-means limited to, the following examples.
  • microcrystalline cellulose To prepare the tablet cores, in a non-shear blender, microcrystalline cellulose,
  • Pregelatinised starch & Mannitol were mixed and to this mixture sodium stearyl fumarate was added and mixed. The mixture is then compressed to tablets of 100 mg each.
  • hydroxypropylmethylcellulose, hydroxypropylcellulose,( polyethylene glycol, titanium dioxide, and talc) were dispersed in water with stirring and the suspension homogenized.
  • ramipril was dispersed in water with stirring and to it hydroxypropylmethylcellulose, hydroxypropylcellulose, (polyethylene glycol, titanium dioxide, and talc) were added. The suspension was homogenized.
  • the outer-coating solution was prepared similar to the seal coat solution. Tablet cores were placed in the coating pan (Hi-Coater) and heated with warm air to an air outlet temperature of about 30°C-45°C. The seal coating solution was sprayed on the cores. Upon completion the heating was discontinued but the air supply was maintained for about 10 minutes in order to dry the tablets.
  • the coated cores were sprayed with the drug coating solution and air dried maintaining the process parameters as for the seal coat. Similarly, the outer coating solution was then sprayed on the drug coated cores.
  • the tablets were air dried and extracted from the apparatus and packed in suitable pack.
  • the particular amounts of ingredients for various formulations are tabulated in Tables I, II III, IV and V. Tablets prepared according to the ingredients of these tables were prepared according to the process described above.
  • Table VII Stability Data of Ramipril Tablets Prepared as per Table IV for 6 Months Stored at 40°C/75% Relative Humidity
  • Table VIII Stability Data of Ramipril+Hydrochlorothiazide Tablets Prepared as per Table V for 6 Months Stored at 40°C/75% Relative Humidity

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Public Health (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Immunology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention concerne des compositions pharmaceutiques stables comprenant un(des) inhibiteur(s) de l'enzyme de conversion ou d'autres substances pharmaceutiquement actives, susceptibles d'être soumises à dégradation, ainsi que des processus permettant de les préparer et des méthodes de traitement impliquant l'administration de compositions de ce type.
PCT/IB2003/000063 2002-01-15 2003-01-14 Compositions pharmaceutiques stables comprenant un(des) inhibiteur(s) de l'enzyme de conversion WO2003059330A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
BR0306928-1A BR0306928A (pt) 2002-01-15 2003-01-14 Composições farmacêuticas estáveis compreendendo inibidores de enzimas conversoras de angiotensina (ace)
EP03729521A EP1467717A1 (fr) 2002-01-15 2003-01-14 Compositions pharmaceutiques stables comprenant un(des) inhibiteur(s) de l'enzyme de conversion
MXPA04006892A MXPA04006892A (es) 2002-01-15 2003-01-14 Composiciones farmaceuticas estables que comprenden inhibidor(es) ace.
US10/501,450 US20050202081A1 (en) 2002-01-15 2003-01-14 Stable pharmaceutical compositions comprising ace inhibitor(s)
AU2003201071A AU2003201071A1 (en) 2002-01-15 2003-01-14 Stable pharmaceutical compositions comprising ace inhibitor(s)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN24/DEL/2002 2002-01-15
IN24DE2002 2002-01-15

Publications (1)

Publication Number Publication Date
WO2003059330A1 true WO2003059330A1 (fr) 2003-07-24

Family

ID=11097019

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2003/000063 WO2003059330A1 (fr) 2002-01-15 2003-01-14 Compositions pharmaceutiques stables comprenant un(des) inhibiteur(s) de l'enzyme de conversion

Country Status (7)

Country Link
US (1) US20050202081A1 (fr)
EP (1) EP1467717A1 (fr)
AR (1) AR038141A1 (fr)
AU (1) AU2003201071A1 (fr)
BR (1) BR0306928A (fr)
MX (1) MXPA04006892A (fr)
WO (1) WO2003059330A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2394660A (en) * 2003-12-17 2004-05-05 Niche Generics Ltd Stabilisation of pharmaceutical compositions comprising ACE inhibitor by absence of acidic excipients having large specific surface area, eg silicon dioxide
WO2005082420A1 (fr) * 2004-02-27 2005-09-09 Niche Generics Limited Composition pharmaceutique stable comportant un inhibiteur ace
WO2005117841A1 (fr) * 2004-05-28 2005-12-15 Bristol-Myers Squibb Company Formulation de comprime revetu et procede correspondant
WO2006038661A1 (fr) * 2004-10-06 2006-04-13 Eisai R & D Management Co., Ltd. Composition medicinale, procede de production de celle-ci, et methode de stabilisation d'un compose de dihydropyridine dans une composition medicinale
WO2006117803A2 (fr) * 2005-03-14 2006-11-09 Devarajan, Padma, Venkitachalam Systemes d'administration transmucosale de medicaments
DE10354862B4 (de) * 2003-01-22 2007-04-26 Sandoz Ag Ramipril enthaltende feste pharmazeutische Zusammensetzungen und Verfahren zu deren Herstellung
ITMI20081313A1 (it) * 2008-07-18 2010-01-19 Univ Degli Studi Milano Sistema per il rilascio al colon di farmaci suscettibili di degradazione enzimatica e/o scarsamente assorbiti nel tratto gastrointestinale
US7829720B2 (en) 2004-05-04 2010-11-09 Bristol-Myers Squibb Company Process for preparing atazanavir bisulfate and novel forms

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WO2005067887A2 (fr) * 2004-03-24 2005-07-28 Actavis Group Formulations de ramipril
GB0518129D0 (en) * 2005-09-06 2005-10-12 Arrow Int Ltd Ramipril formulation
US20070098782A1 (en) * 2005-10-28 2007-05-03 Selamine Limited Ramipril Formulation
GB2431579A (en) * 2005-10-28 2007-05-02 Arrow Int Ltd Ramipril formulations
WO2008001184A2 (fr) * 2006-06-26 2008-01-03 Emcure Pharmaceuticals Limited Composition solide
GB0624084D0 (en) * 2006-12-01 2007-01-10 Selamine Ltd Ramipril amino acid salts
GB0624090D0 (en) * 2006-12-01 2007-01-10 Selamine Ltd Ramipril amine salts
GB0624087D0 (en) * 2006-12-01 2007-01-10 Selamine Ltd Ramipril combination salt
TR200906322A2 (tr) 2009-08-17 2011-07-21 Bi̇lgi̇ç Mahmut Çözünürlük ve stabilite özellikleri geliştirilmiş granüller.
ES2364011B1 (es) 2009-11-20 2013-01-24 Gp Pharm, S.A. Cápsulas de principios activos farmacéuticos y ésteres de ácidos grasos poliinsaturados para el tratamiento de enfermedades cardiovasculares.

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US4800084A (en) * 1984-02-01 1989-01-24 Horst Zerbe Pharmaceutical product in the form of a pellet with continuous, delayed medicament substance emission
EP0309051A1 (fr) * 1987-09-24 1989-03-29 Merck & Co. Inc. Pompe osmotique à porosité contrôlée
US5158777A (en) * 1990-02-16 1992-10-27 E. R. Squibb & Sons, Inc. Captopril formulation providing increased duration of activity
US6086919A (en) * 1994-09-02 2000-07-11 Astra Aktiebolag Pharmaceutical composition containing the ace inhibitor ramipril and a dihydropyridine compound
US6004582A (en) * 1997-05-30 1999-12-21 Laboratorios Phoenix U.S.A, Inc. Multi-layered osmotic device
WO2001051037A1 (fr) * 2000-01-13 2001-07-19 Osmotica Corp. Dispositif osmotique contenant du diltiazem et un inhibiteur de l"ace ou un diuretique

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10354862B4 (de) * 2003-01-22 2007-04-26 Sandoz Ag Ramipril enthaltende feste pharmazeutische Zusammensetzungen und Verfahren zu deren Herstellung
GB2394660A (en) * 2003-12-17 2004-05-05 Niche Generics Ltd Stabilisation of pharmaceutical compositions comprising ACE inhibitor by absence of acidic excipients having large specific surface area, eg silicon dioxide
WO2005082420A1 (fr) * 2004-02-27 2005-09-09 Niche Generics Limited Composition pharmaceutique stable comportant un inhibiteur ace
US8513428B2 (en) 2004-05-04 2013-08-20 Bristol-Meyers Squibb Company Process for preparing atazanavir bisulfate and novel forms
US7829720B2 (en) 2004-05-04 2010-11-09 Bristol-Myers Squibb Company Process for preparing atazanavir bisulfate and novel forms
EP2298288A1 (fr) * 2004-05-28 2011-03-23 Bristol-Myers Squibb Company Formulation de comprime revêtu et procède correspondant
US8628799B2 (en) 2004-05-28 2014-01-14 Bristol-Myers Squibb Company Coated tablet formulation and method
JP2008501025A (ja) * 2004-05-28 2008-01-17 ブリストル−マイヤーズ　スクイブ　カンパニー コートされた錠剤処方および方法
RU2372894C2 (ru) * 2004-05-28 2009-11-20 Бристол-Маерс Сквибб Компани Покрытая таблетка и способ ее получения
NO343907B1 (no) * 2004-05-28 2019-07-01 Astrazeneca Ab Belagt tablett og fremgangsmåte for fremstilling derav
EP2298288B2 (fr) † 2004-05-28 2019-04-03 AstraZeneca AB Formulation de comprime revêtu et procède correspondant
EP3078369A1 (fr) * 2004-05-28 2016-10-12 Astrazeneca AB Formulation de comprimé revêtu et procédé correspondant
AU2005249467B2 (en) * 2004-05-28 2010-10-21 Astrazeneca Ab Coated tablet formulation and method
EP2298288B1 (fr) 2004-05-28 2016-06-22 AstraZeneca AB Formulation de comprime revêtu et procède correspondant
US9339472B2 (en) 2004-05-28 2016-05-17 Astrazeneca Ab Coated tablet formulation and method
US7951400B2 (en) 2004-05-28 2011-05-31 Bristol-Myers Squibb Company Coated tablet formulation and method
JP4901727B2 (ja) * 2004-05-28 2012-03-21 ブリストル−マイヤーズ スクイブ カンパニー コートされた錠剤処方および方法
CN1988891B (zh) * 2004-05-28 2012-11-28 布里斯托尔-迈尔斯斯奎布公司 包衣片制剂和方法
CN102895208A (zh) * 2004-05-28 2013-01-30 布里斯托尔-迈尔斯斯奎布公司 包衣片制剂和方法
KR101290925B1 (ko) 2004-05-28 2013-07-29 브리스톨-마이어스 스큅 컴퍼니 코팅된 정제 제형 및 방법
WO2005117841A1 (fr) * 2004-05-28 2005-12-15 Bristol-Myers Squibb Company Formulation de comprime revetu et procede correspondant
EP1753406B1 (fr) 2004-05-28 2016-04-20 AstraZeneca AB Formulation de comprime revetu et procede correspondant
CN102895208B (zh) * 2004-05-28 2015-05-13 阿斯利康(瑞典)有限公司 包衣片制剂和方法
WO2006038661A1 (fr) * 2004-10-06 2006-04-13 Eisai R & D Management Co., Ltd. Composition medicinale, procede de production de celle-ci, et methode de stabilisation d'un compose de dihydropyridine dans une composition medicinale
WO2006117803A3 (fr) * 2005-03-14 2007-01-25 Devarajan Padma Venkitachalam Systemes d'administration transmucosale de medicaments
WO2006117803A2 (fr) * 2005-03-14 2006-11-09 Devarajan, Padma, Venkitachalam Systemes d'administration transmucosale de medicaments
WO2010007515A3 (fr) * 2008-07-18 2010-03-25 Maria Edvige Sangalli Système pour l'administration de médicaments par le côlon sous réserve de la dégradation enzymatique et/ou faiblement absorbés dans le tractus gastro-intestinal
WO2010007515A2 (fr) 2008-07-18 2010-01-21 Maria Edvige Sangalli Système pour l'administration de médicaments par le côlon sous réserve de la dégradation enzymatique et/ou faiblement absorbés dans le tractus gastro-intestinal
ITMI20081313A1 (it) * 2008-07-18 2010-01-19 Univ Degli Studi Milano Sistema per il rilascio al colon di farmaci suscettibili di degradazione enzimatica e/o scarsamente assorbiti nel tratto gastrointestinale

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AR038141A1 (es) 2004-12-29
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US20050202081A1 (en) 2005-09-15
EP1467717A1 (fr) 2004-10-20
BR0306928A (pt) 2004-11-09

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